This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Influenza B virus (IBV) is more likely to cause complications than influenza A virus (IAV) and even causes higher disease burden than IAV in a certain season, but IBV has received less attention. In order to analyze the genetic evolution characteristics of the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018), we constructed genetic evolution trees and analyzed the homology and different amino acids of hemagglutinin and neuraminidase referring to the vaccine strains recommended by World Health Organization (WHO). We found that strain B/Guangxi-Jiangzhou/1352/2018 was free of interlineage reassortment and poorly matched with the vaccine strain B/Colorado/06/2017 of the same year. We also determined the median lethal dose (LD₅₀) and the pathogenicity of strain B/Guangxi-Jiangzhou/1352/2018 in mice. The results showed that the LD₅₀ was 10^5.9 TCID₅₀ (median tissue culture infective dose), the IBV titer in the lungs reached peak 1 d post infection and the mRNA level of the most of inflammatory cytokines in the lungs reached peak 12 h post infection. The alveoli in the lungs were severely damaged and a large number of inflammatory cells were infiltrated post infection. The study demonstrated that the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018) could infect mice and induce typical lung inflammation. This will facilitate the research on the pathogenesis and transmission mechanism of IBV, and provide an ideal animal model for evaluation of new vaccines, antiviral and anti-inflammatory drug.
Amino Acids/genetics* ; Animals ; Antiviral Agents/pharmacology* ; China ; Cytokines/metabolism* ; Hemagglutinins/metabolism* ; Humans ; Influenza B virus/pathogenicity* ; Influenza, Human/virology* ; Mice ; Neuraminidase/genetics* ; Orthomyxoviridae Infections/virology* ; Phylogeny ; RNA, Messenger/metabolism* ; Virulence/genetics*

This study aimed to understand the differences in clinical, epidemiological, and laboratory features between the new coronavirus disease 2019 (COVID-2019) and influenza A in children. Data of 23 hospitalized children with COVID-19 (9 boys, 5.7 ± 3.8 years old) were compared with age- and sex-matched 69 hospitalized and 69 outpatient children with influenza A from a hospital in China. The participants' epidemiological history, family cluster, clinical manifestations, and blood test results were assessed. Compared with either inpatients or outpatients with influenza A, children with COVID-19 showed significantly more frequent family infections and higher ratio of low fever (< 37.3 °C), but shorter cough and fever duration, lower body temperature, and lower rates of cough, fever, high fever (> 39 °C), nasal congestion, rhinorrhea, sore throat, vomiting, myalgia or arthralgia, and febrile seizures. They also showed higher counts of lymphocytes, T lymphocyte CD8, and platelets and levels of cholinesterase, aspartate aminotransferase, lactate dehydrogenase, and lactic acid, but lower serum amyloid, C-reactive protein, and fibrinogen levels and erythrocyte sedimentation rate, and shorter prothrombin time. The level of alanine aminotransferase in children with COVID-19 is lower than that in inpatients but higher than that in outpatients with influenza A. Pediatric COVID-19 is associated with more frequent family infection, milder symptoms, and milder immune responses relative to pediatric influenza A.
Betacoronavirus ; physiology ; Case-Control Studies ; Child ; Coronavirus Infections ; blood ; epidemiology ; immunology ; virology ; Female ; Humans ; Influenza, Human ; blood ; epidemiology ; immunology ; Male ; Pandemics ; Pneumonia, Viral ; blood ; epidemiology ; immunology ; virology

Objective: Interferon-induced transmembrane protein 3 (IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection . Methods: We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer (NK) cell numbers, their activation, and their immune function in the lungs of -/- and wild-type mice. Results: -/- mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of -/- mice during acute influenza infection. Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in -/- mice.
Acute Disease ; Animals ; Disease Models, Animal ; Female ; Humans ; Influenza, Human ; virology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections ; veterinary ; virology ; Rodent Diseases ; virology

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Birds ; virology ; Child ; Child, Preschool ; Global Warming ; Humans ; Infant ; Influenza A virus ; Influenza, Human ; epidemiology ; Middle Aged ; Orthomyxoviridae Infections ; epidemiology ; Temperature ; Young Adult

BACKGROUND: Six epidemic waves of human infection with avian influenza A (H7N9) virus have emerged in China with high mortality. However, study on quantitative relationship between clinical indices in ill persons and H7N9 outcome (fatal and non-fatal) is still unclear. A retrospective cohort study was conducted to collect laboratory-confirmed cases with H7N9 viral infection from 2013 to 2015 in 23 hospitals across 13 cities in Guangdong Province, China. METHODS: Multivariable logistic regression model and classification tree model analyses were used to detect the threshold of selected clinical indices and risk factors for H7N9 death. The receiver operating characteristic curve (ROC) and analyses were used to compare survival and death distributions and differences between indices. A total of 143 cases with 90 survivors and 53 deaths were investigated. RESULTS: Average age (Odds Ratio (OR) = 1.036, 95% Confidence Interval (CI) = 1.016-1.057), interval days between dates of onset and confirmation (OR = 1.078, 95% CI = 1.004-1.157), interval days between onset and oseltamivir treatment (OR = 5.923, 95% CI = 1.877-18.687), body temperature (BT) (OR = 3.612, 95% CI = 1.914-6.815), white blood cell count (WBC) (OR = 1.212, 95% CI = 1.092-1.346) were significantly associated with H7N9 death after adjusting for confounders. The chance of death from H7N9 infection was 80.0% if BT was over 38.1 °C, and chance of death is 67.4% if WBC count was higher than 9.5 (10/L). Only 27.1% of patients who began oseltamivir treatment less than 9.5 days after disease onset died, compared to 68.8% of those who started treatment more than 15.5 days after onset. CONCLUSIONS The intervals between date of onset and confirmation of diagnosis, between date of onset to oseltamivir treatment, age, BT and WBC are found to be the best predictors of H7N9 mortality.
Adult ; Aged ; China ; epidemiology ; Confidence Intervals ; Female ; Hospitalization ; statistics & numerical data ; Humans ; Influenza A Virus, H7N9 Subtype ; pathogenicity ; Influenza, Human ; epidemiology ; mortality ; virology ; Logistic Models ; Male ; Middle Aged ; ROC Curve ; Retrospective Studies ; Risk Factors ; Young Adult

We report and analyze the clinical data of the first case of severe pneumonia caused by influenza B virus from swine. The patient, a 62 year-old male domestic pig breeder, was admitted to hospital because of fever and muscle pain for 5 days, and anhelation for 3 days. One week before the onset of disease, the patient kept close contact with pigs. CT scan of the chest showed diffuse infiltration in both lungs. Influenza B virus antigen detection (colloidal gold method) was repeatedly positive. These all confirmed influenza B virus infection. Poor appetite, weight loss, cough, poor spirit of pigs, positive influenza B virus antigen test occurred in the pig, while the patient had no history of exposure to influenza B-infected patients. It was likely that influenza B virus was transmitted from domestic pigs to the patient by droplets or close contact. Influenza B virus epidemics always occur every five or six years a time, and patients and carriers are the main source of infection. After searching the Pubmed, Web of science, Elsevier, Wanfang, and CNKI databases, it was found that although there were many studies on influenza B virus infecting seals, ferret, domestic pigs, guinea pigs, and other animals, there was no case report for animal-to-human infection. It is the first case report of type B influenza virus transmission from domestic pigs to people in the world, which provides a new direction for the research and prevention of influenza B virus.
Animals ; Humans ; Influenza B virus ; Influenza, Human ; complications ; etiology ; virology ; Lung ; virology ; Male ; Middle Aged ; Orthomyxoviridae Infections ; transmission ; Pneumonia ; etiology ; Swine ; Swine Diseases ; transmission ; virology

Objective: To understand the epidemiological characteristics of human infection with avian influenza A (H7N9) virus in China, and provide evidence for the prevention and control of human infection with H7N9 virus. Methods: The published incidence data of human infection with H7N9 virus in China from March 2013 to April 2017 were collected. Excel 2007 software was used to perform the analysis. The characteristics of distribution of the disease, exposure history, cluster of the disease were described. Results: By the end of April 2017, a total of 1 416 cases of human infection with H7N9 virus were confirmed in China, including 559 deaths, the case fatality rate was 39.5%. In 2016, the case number was lowest (127 cases), with the highest fatality rate (57.5%). The first three provinces with high case numbers were Zhejiang, Guangdong and Jiangsu. The median age of the cases was 55 years and the male to female ratio was 2.3∶1. Up to 66% of cases had clear live poultry exposure history before illness onset, 31% of cases had unknown exposure history and only 3% of the cases had no live poultry exposure history. There were 35 household clusters (5 in 2013, 9 in 2014, 6 in 2015, 5 in 2016, 10 in 2017), which involved 72 cases, accounting for 5% of the total cases. Conclusions: The epidemic of human infection with H7N9 virus in China during 2013-2017 had obvious seasonality and spatial distribution. There was limited family clustering. Infection cases were mostly related to poultry contact.
Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Animals ; China/epidemiology* ; Cluster Analysis ; Disease Outbreaks ; Epidemics ; Female ; Humans ; Incidence ; Influenza A Virus, H7N9 Subtype/isolation & purification* ; Influenza, Human/virology* ; Male ; Middle Aged ; Poultry ; Sex Distribution

Objective: To study the willingness and influence factors related to "centralized slaughtering, fresh poultry listing and marketing" strategy, among the household chefs, and provide reference for government to adjust and optimize the strategy on avian influenza prevention. Methods: According to the geographical characteristics and regional functions, 6 'monitoring stations' were selected from 12 residential districts of Guangzhou, respectively. Another 21 meat markets which selling live poultry, were selected in each station and 5 household chefs of each market were invited to attend a face to face interview. Basic information, personal cognitive, willingness and influencing factors to the policy were under study. Univariate and multivariate logistic regression methods were used. Results: A total of 664 household chefs underwent the survey and results showed that the rate of support to the "centralized slaughtering, fresh poultry listing and marketing" strategy was 44.6% (296/664). Results from the multi-factor logistic regression showed that those household chefs who were males (OR=1.618, 95% CI: 1.156-2.264, P=0.005), having received higher education (OR=1.814, 95% CI: 1.296-2.539, P=0.001), or believing that the existence of live poultry stalls was related to the transmission of avian influenza (OR=1.918, 95% CI: 1.341-2.743, P<0.001) were factors at higher risk. These household chefs also intended to avoid the use of live poultry stalls (OR=1.666, 95%CI: 1.203-2.309, P=0.002) and accept the "centralized slaughtering, fresh poultry listing and marketing" strategy. Conclusion: Detailed study on this subject and, setting up pilot project in some areas as well as prioritizing the education programs for household chefs seemed helpful to the implementation of the 'freezing-fresh poultry' policy.
Animals ; Attitude to Health ; China ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza in Birds ; Influenza, Human/prevention & control* ; Male ; Marketing ; Meat-Packing Industry ; Multivariate Analysis ; Pilot Projects ; Poultry/virology* ; Surveys and Questionnaires

Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.
Animals ; Chickens ; China ; Commerce ; Humans ; Influenza A Virus, H7N9 Subtype/pathogenicity* ; Influenza in Birds/virology* ; Influenza, Human/virology* ; Phylogeny ; Poultry/virology* ; Real-Time Polymerase Chain Reaction ; Zoonoses